A New Lipid Based Drug Delivery System (LBDDS) for Oral Delivery of Tioconazole

anthony attama, igwebuike ayogu, franklin kenechukwu, john ogbonna, vincent okore


Purpose: Peroral delivery of some drugs with limited aqueous solubility has remained a challenge to drug formulation experts. This work seeks to address the issue of unavailability of oral delivery system of tioconazole, a potent antifungal agent.

Method: Novel lipid based drug delivery systems (LBDDS) of tioconazole, composed of oil, surfactants and co-surfactants were  formulated and  their physicochemical as well as pharmacokinetic parameters determined. The oil, surfactant and co-surfactant used were soya bean oil, Cremophor® S9 and Brij® 35, respectively. The droplet sizes of the tioconazole micro-emulsion obtained after self emulsification were assessed after 72 h incubation. The in vitro permeation studies of the tioconazole-loaded LBDDS were evaluated using a modified Franz cell.

Result: Permeation  coefficients of the formulation were between 1.204 x 10-3 cm/sec and 2.178 x 10-3 cm/sec. In vitro microbiological test of the tioconzole LBDDS revealed increased in vitro antifungal activity (≈ 1.4 times) against clinically isolated Candida albicans as compared to tioconazole solution. Preliminary in vivo pharmacokinetic studies also showed an AUC∞-12 of 2930 µg/hr/ml for the optimized LBDDS formulation while that of oral suspension was 1171 µg/hr/ml and the  Cmax of the optimized LBDDS formulation was 797 µg/ml  as against 355 µg/ml obtained for the pure drug. This showed a 2.5-fold increase in the systemic bioavailability of tioconazole from the optimized LBDDS formulation.

Conclusion: The result of this study gave insight that the issue of unavailability of tioconazole in oral delivery system could be surmounted by tactical engineering of  LBDDS such as self-microemulsifying drug delivery systems (SMEDDS).


tioconazole; bioavailability; LBDDS; Cremophor®S9; Brij®35; permeation coefficient.

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Jevons S, Gymer GE, Brammer KW, Cox DA, Leeming MRG. Antifungal activity of tioconazole (Uk-20,349), a new imidazole derivative. Antimicrob. Agents Chemother.1979;15:597-602.

Odds FC. Laboratory evaluation of antifungal agents; a comparative study of five imidazole derivatives of clinical importance. J. Antimicrob. Chemother. 1980;6:749-761.

Clissold SP, Heel RC. Tioconazole: A review of its antimicrobial activity and therapeutic use in superficial mycoses. Drugs. 1986;31:29-51.

Beggs WH. Fungicidal activity of tioconazole in relation to growth phase of Candida albicans and Candida parapsilosis. Antimicrob. Agent Chemother. 1984;26:699-701.

Wakerly MG, Pouton CW, Meakin BJ. Evaluation of the self emulsifying performance of a non-ionic surfactant– vegetable oil mixture. J. Pharm. Pharmacol. 1987;39:6.

Charman SA, Charman WN, Rogge MC, Wilson TD, Pouton CW. Self emulsifying drug delivery systems: Formulation and biopharmaceutical evaluation of an investigational lipophilic compound. Pharm. Res. 1992;9:87-93.

Craig DQM. An investigation into the physico-chemical properties of self emulsifying systems using low frequency dielectric spectroscopy, surface tension measurement and particle size analysis. Int. J. Pharm. 1993;96:147-155.

Shah NH, Carvajal MT, Patel CL, Infeld NH, Malick AW. Self emulsifying drug delivery systems (SEDDS) with polyglycolized glycerides for improving in vitro dissolution and oral absorption of lipophilic drugs. Int. J. Pharm. 1994;106:15-23.

Holm R, Poter CJH, Edward GA, Mullertz A, Kristenset HG and Charman WW. Examination of oral absorption and lymphatic transport of halofantrine in a tripple canulated canin model after administration of self microemulsifying drug delivery system (SMEDDS) containing structured triglycerides. Eur. J. Pharm. Sci. 203;20:91-97.

Shi S, Chen H, Lin X, Tang X. Pharmacokinetic , tissue distribution and safety of cinnarizine delivered in lipid emulsion. Int. J. Pharm. 2010;383:264-270.

Hai-Rong S, Ming-Kang Z. Preparation and evaluation of SMEDDS containing atovastatin. J. Pharm. Pharmacol. 2006;58:1183-1191.

Patel D, Kurutika KS. Oral bioavailability enhancement of acyclovir by SMEDDS. Drug Dev. Ind. Pharm. 2007;33:1318-1326.

Pierard GE, Arrese JE, Quatresooz P. Emerging therapeutic agents for onychomycosis. Expert Opinion Emerging Drugs 2007;12(3):345-53.

Canuto MM, Crutierrez F. Antifungal resistance to a azoles and polyenes. Lancet Infect. Dis. 2002;2(9):500-63.

Chan OH, Stewart BH. Physiochemical and drug delivery consideration for oral drug bioavailability. Drug Discov. Today. 1996;1(11):461-473.

Edmund MB, Wallace SE, McClish DK. Nosocomial blood stream infections in United State hospitals, a three year analysis. Clin. Infect. Dis. 1999;29(3):239-244.

Blyth CC, Palasanthiran P, O’Brien TA. Antifungal therapy in children with invasive fungal infections: A systematic review. Pediatrics. 2007;119:772-784.

Zaoutis TE, Heydon K, Chu JH, Walsh TJ, Sheinbach WJ. Epidemiology, outcomes and costs of invasive aspergillosis in immunocompromised children in the United States 2000. Paediatrics. 2006;117:e711-e716.

Zaoutis TE, Heydon K, Localio R, Walsh TJ, Feudtner C. Outcomes attributable to neonatal candidiasis. Clin. Infect. Dis. 2007;44:1187-1193.

Smith PB, Morgan J, Benjamin JD. Excess cost of hospital care associated with neonatal candidemia. Paediatr. Infect. Dis. J. 2007;26:197-200.

Steinbach WJ. Pediatric aspergillosis; disease and treatment differences in children. Pediatric Infect. Dis. J. 2005;24:358-364.

Kim J-K, Park J-S, Kim C-K. Development of a binary lipid nanoparticles formulation of itraconzole for parenteral administration and controlled release. Int. J. Pharm. 2010;383:209-215.

Bachynsky MO, Shah NH, Patel CI, Malick AW. Factors affecting the efficiency of self-emulsifying oral delivery system. Drug Dev. Ind. Pharm. 1997;23 (8):809-816.

Solis D, Enrique V, Sussana H, Antonio G, Manuel A. Textural, structural and electrical properties of TiO2 Nanoparticles using Brij® 35 and P123 as surfactants. Sci. Technol. Adv. Mater. 2008; 9:025003 doi:10.1088/1468-6996/9/2025003.

Attama AA, Reichl S, Müller-Goyman, CC. Diclofenac sodium delivery to the eye: In vitro evaluation of novel solid lipid nanoparticle formulation using human cornea construct. Int. J. Pharm. 2008;355:307 – 313.

Verreck G, Brewster ME. Melt extrusion-based dosage forms: excipients and processing conditions for pharmaceutical formulations. Bull. Tech. Gattefossé 2004;97:85-95.

Porter CJH, Charman, WN. Uptake of drug into the intestinal lymphatics after oral administration. Adv. Drug. Deliv. Rev. 2007;25:71-89.


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